Effects of Total Flavones from Acanthopanax senticosus on L‐type Calcium Channels, Calcium Transient and Contractility in Rat Ventricular Myocytes

Abstract

Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L-type Ca(2+) channel currents (ICa-L ) using the whole cell patch-clamp technique and on intracellular calcium ([Ca(2+) ]i ) handling and cell contractility in rat ventricular myocytes with the aid of a video-based edge-detection system. Exposure to TFAS resulted in a concentration- and voltage-dependent blockade of ICa-L , with the half-maximal inhibitory concentration (IC50 ) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current-voltage relationship but also shifted the activation and inactivation curves of ICa-L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca(2+) ]i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca(2+) ]i through the direct inhibition of ICa-L in rat ventricular myocytes and consequent negative effect on myocardial contractility.

New Findings on the Effects of Tannic Acid: Inhibition of L‐Type Calcium Channels, Calcium Transient and Contractility in Rat Ventricular Myocytes

“…I Ca‐L was elicited under the steady‐state activation protocol. NiCl 2 (0.1 mM), a specific T‐type calcium channel blocker, had no influence on the currents, which showed that these currents were not T‐type Ca 2+ currents (Guan et al ., ). Beyond that, 0.01 mM nicardipin, a specific L‐type calcium channel blocker (Ren et al ., ), almost completely blocked the I Ca‐L , which showed that these currents were I Ca‐L in rat ventricular myocytes.…”

Acanthopanax senticosus Induces Vasorelaxation via Endothelial Nitric Oxide-Dependent and -Independent Pathways

“…ASRE may directly relax vascular smooth muscle by inhibiting Ca 2+ channels or contraction pathways based on the result showing a reduction in vasoconstriction induced by an alphaadrenergic agonist and depolarization with high KCl in the presence of ASRE. Total flavones from A. senticosus reduce intracellular Ca 2+ by directly inhibiting L-type Ca 2+ channel currents in rat ventricular myocytes, resulting in a negative effect on myocardial contractility [18]. Furthermore, the possibility of hyperpolarization via K + channel opening cannot be excluded because Kwan et al (2004) suggested the involvement of EDHF in the vascular effects of ASRE; ASRE-induced relaxation in the Phenyl-precontracted rat aorta was completely reversed by 5 mM tetraethylammonium chloride [14].…”

In VivoEvaluation of the Antiasthmatic, Antitussive, and Expectorant Activities and Chemical Components of ThreeElaeagnusLeaves

“…The results indicates that it mainly contains many flavonoids of which the chemical structures are characterized by quercetin, kaempferol, and isorhamnetin as aglycones linking with glycosyl groups [18, 19]. Many other researches have verified that flavonoids from Chinese herbs are effective on antiasthmatic, antitussive, and expectorant properties, for example, naringenin from Exocarpium Citri Grandis and total flavones from Acanthopanax senticosus [26–29]. Moreover, plants from Elaeagnus are reported to have flavonoid constituents such as E. henryi , E. lanceolata , E. angustifolia, and E. bockii [8–10, 21].…”